Target intelligence / Profile preview

Hypoxia-inducible factor (HIF) pathway (HIF pathway)

Target
HIF pathway
Molecular classification
Transcription factor, Signaling pathway, Enzyme
01

Overview

The tissue hypoxia response pathways encompass a group of highly conserved cellular mechanisms that detect and respond to low oxygen availability. Central to this process are hypoxia-inducible factors (HIFs), which are transcription factor complexes that regulate the expression of hundreds of genes involved in adaptation to hypoxia, including those governing angiogenesis, metabolism, cell survival, and immune regulation. The response involves complex signaling networks (HIF pathway, unfolded protein response, mTOR signaling, and others) that alter cell behavior in physiological and pathological contexts, such as development, cancer, inflammation, cardiovascular, and pulmonary diseases. Modulation of these pathways—particularly through selective inhibition or activation of components like HIF-1α or HIF-2α—is a current therapeutic strategy in conditions ranging from anemia to cancer

Other names
Hypoxic response pathwayCellular hypoxia signalingOxygen sensing pathwayHIF signaling pathway
02

Mechanism of action

Inhibition of HIF prolyl hydroxylases (preventing HIF degradation, increasing HIF activity); Inhibition of HIF-2α dimerization (reducing HIF-2-mediated gene transcription)

03

Biological functions

Cellular adaptation to low oxygenGene regulation (transcriptional activation of hypoxia-responsive genes)Angiogenesis (new blood vessel formation)Metabolic reprogramming (shift to anaerobic metabolism, glycolysis)Immune response regulationRegulation of cell proliferation, apoptosis, and survival
04

Disease associations

Cancer (tumor hypoxia, angiogenesis, chemoresistance)Cardiovascular disease (ischemia, tissue injury responses)Inflammatory disease (arthritis, atherosclerosis, autoimmunity)Infection (host-pathogen adaptation)Pulmonary hypertensionStroke and ischemic disorders
05

Safety considerations

Polycythemia (increased red blood cells)Thromboembolic riskPotential for tumor progression (activation of angiogenesis in cancer)
06

Interacting drugs

Roxadustat

4 more in the full profile.

07

Biomarkers

HIF-1α and HIF-2α protein levelsVascular endothelial growth factor (VEGF)Serum lactateErythropoietin (EPO)Carbonic anhydrase IX (CA9)

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